Rapid eye movement (REM) sleep is a stage of sleep constituted by the concurrent appearance of many physiological processes and comprises about 20% of total sleep in adult humans. Despite research efforts for over 50 years utilizing modern neuroscience techniques, the biological functions or brain mechanisms subserving initiation and maintenance of this unique state of arousal are incompletely understood. The proposed project addresses the neural mechanisms that control and modulate the expression of REM sleep. Evidence supports REM sleep to be dependent on a set of anatomically distributed neural mechanisms. The sublaterodorsal nucleus (SLD), in the brainstem, is a REM sleep induction zone where the local application of GABAA receptor antagonists can result in the rapid onset of REM sleep. This implicates GABA, in interaction with mechanisms in SLD, to be involved in a negative-control of natural REM sleep. Several recent theories of REM sleep physiology put GABAergic action in SLD as central to the mechanisms controlling REM sleep expression. Yet, there are certain gaps in our knowledge that need to be filled to either support or refute these novel concepts. The objective of the current proposal is to test hypotheses relating to the nature of the GABAergic input to SLD from its two major sources, the caudal nucleus pontis oralis (PnOc) and, what we will call, the lateral pontine tegmentum (LPT). Anatomical and functional- anatomical histochemical methods, as well as behavioral pharmacology, in rat, will address the following questions: 1. Do the GABAergic neurons projecting to SLD have a REM sleep-related pattern of activation; 2. How is the GABAergic innervation of SLD organized and what receptor subtypes mediate action on REM sleep; and 3. What types of neurons in SLD receive the GABAergic input. Answers to these questions will permit a basic evaluation of the role of GABA in SLD in control of REM sleep and yield a better understanding of the mechanisms mediating sleep-state control at the cellular level. Information concerning these control mechanisms are essential to understanding the physiological process manifested during both normal and pathological sleep/wake states. PUBLIC HEALTH RELEVANCE: Project's Health Relatedness - The proposed research project is directed to the understanding of the mechanisms of REM sleep, which can have a direct impact on several serious sleep disorders such as narcolepsy, REM sleep behavior disorders and REM-related parasomnias. Pathophysiology in REM sleep mechanisms has been hypothesized to be centrally involved in post traumatic stress disorder as well as major depressive disorder . Selective deprivation of REM sleep results in a significant improvement of symptoms in depression. Studies have shown that REM sleep measures during treatment for alcoholism are significant factors predicting risk of relapse. This further supports an involvement of REM sleep mechanisms in drug abuse, but specifically how remains unclear. This research proposal hopes to contribute to our knowledge on the role of REM sleep mechanisms in the etiology and reinforcement of these disorders.